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The role of chromosome stability in persistence, latency and reactivation of Mycobacterium tuberculosis
Framework programme:
Project number:
EC contribution:
€ 1,000,000
24 months
Starting date:
January 2007

Keywords: Tuberculosis, Latency, DNA Repair, Microbiology, Biochemistry, Molecular Biology


Tuberculosis (TB) causes more deaths than almost any other infectious disease, with nearly 2 million deaths each year. It is estimated that one-third of the world's population is latently infected with the causative agent, Mycobacterium tuberculosis. The ability of M. tuberculosis to enter into a latent state is thought to be the reason for the prolonged period of treatment required to prevent relapse, since drugs currently available mainly target actively growing bacteria.

The vast pool of latently infected individuals is a constant source of disease and transmission, as factors weakening the immune response, such as HIV infection, lead to the emergence of active disease. There is evidence that M. tuberculosis is exposed to DNA-damaging conditions in the host during latent infection. It is hypothesized that M. tuberculosis possesses particularly efficient mechanisms of DNA repair, and that these systems are required for the longterm survival of M. tuberculosis within the host. This project aims to evaluate the importance of the mechanisms which maintain genome integrity for bacterial survival during persistence and to identify targets for future drug development.

The proposal integrates activities of internationally recognised groups in the field that have complementary expertise to facilitate the multidisciplinary approach required to optimally advance this programme of research. Identification of inhibitors of proteins required for persistence is likely to lead to the development of new drugs active against bacteria in the latent state. This would be of great value both to shorten the period required to cure the active disease and to treat latent infection in individuals at high risk of disease reactivation.

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